No description available.

Instrumentos de avaliação da memória episódica não verbal são escassos. Além disto, consideramos a crescente necessidade de esforços para a adaptação transcultural de instrumentos de memória para nosso contexto. O subteste Visual Reproduction I e II (Reprodução Visual I e II) faz parte da Wechsler Memory Scale (WMS) e se trata de uma escala mundialmente utilizada e adaptada a diversas culturas, sendo considerada padrão ouro dentre as medidas de avaliação da memória. No presente estudo, utilizamos o subteste Reprodução Visual, da WMS na sua quarta edição (WMS-IV). O Reprodução Visual (RV) é subdividido em três domínios de investigação da memória visual (evocação imediata, evocação tardia e reconhecimento) e uma tarefa opcional para avaliação da percepção visual, habilidades construtivas e atenção aos detalhes (cópia). Além disto, o escore de cada um dos três domínios avaliados podem ser contrastados, de modo que se obtenham informações sobre a retenção, o quanto a memória é melhor ou pior do que as habilidades construtivas e, por último, o quão o sujeito evoca livremente ou precisa de pistas para evocar a informação aprendida. Esta versão da WMS-IV é uma revisão da WMS-III, cujos estudos resultaram em algumas alterações metodológicas e de conteúdo, no sentido de facilitar a análise dos resultados, diminuir os vieses de aplicação e correção. Desta forma, para atingir os propósitos desta pesquisa foram realizados dois estudos: o Estudo 1 teve como objetivo realizar a adaptação transcultural do subteste Visual Reproduction I and II - Wechsler Memory Scale IV (WMS-IV) e apresentar uma versão para uso preliminar no Brasil. O estudo 2 consistiu na avaliação das suas propriedades psicométricas. Participaram do estudo 1 três tradutores com fluência no inglês, que realizaram traduções independentes, dois tradutores profissionais e dois juízes especialistas (um neurologista e uma neuropsicóloga). Os juízes especialistas e um tradutor profissional investigaram a equivalência conceitual, semântica e operacional dos itens. Uma amostra de 24 sujeitos saudáveis responderam ao pré-teste, que consistiu na investigação da compreensão e dificuldade da versão adaptada do Reprodução Visual I e II. No estudo dois, participaram 62 adultos saudáveis e 29 adultos com Acidente vascular cerebral em hemisfério direito, no território da Artéria cerebral média (AVC-ACMHD). Os sujeitos tinham idade entre 20 e 59 anos e as respostas foram consideradas para análises de confiabilidade e validade baseadas em análises estatísticas da teoria clássica (ANOVA, ANCOVA, coeficiente alfa de Cronbach, e correlação de Pearson) e da teoria moderna de testagem (Teoria de Resposta ao Item (TRI) através do modelo de um parâmetro ou método de Rasch). O processo de análise das propriedades psicométricas utilizou a metodologia recomendada pelo American Educational Research Association [AERA], American Psychological Association [APA] e o National council on measure in education [NCME], 2008 indicada pela editora responsável pelos direitos autorais do WMS-IV. Na confiabilidade, foi investigada a consistência interna (coeficiente alfa de Cronbach) e a estabilidade temporal (correlação de Pearson). Na investigação da validade, foram investigados: os processos de resposta, a estrutura interna (correlação de Pearson, Teoria de resposta ao Item pelo método de Rash), a relação com outros instrumentos (Mini Exame do Estado Mental - MEEM e Figuras Complexas de Rey) e a relação com variáveis externas (AVC-ACMHD comparados a controles saudáveis). O índice de consistência interna do subteste foi de 0,92 e a estabilidade teste-reteste mostrou correlação significativa, exceto com a tarefa de evocação tardia. Esses resultados são similares aos do estudo original, sendo, portanto caracterizada a sua equivalência. Os resultados do estudo de validade mostraram que há equivalência em termos de conteúdo.A investigação da estrutura interna pelo coeficiente de correlação de Pearson evidenciou que todas as figuras obtiveram correlação significativa (p<0,001). Ainda mais: correlacionaram-se congruentemente durante toda a tarefa. Na investigação da estrutura interna pelo método de Rasch foi evidenciado que o teste é unidimensional, que a progressão de theta ao longo das categorias de resposta foram como o esperado pelo modelo. A TRI mostrou que a figura mais fácil é a figura 1 da tarefa de evocação imediata e a mais difícil é a figura 5 de evocação tardia. Os índices de correlação theta foram superiores a 0,5, mostrando correlação. No mapa de pessoas-itens as variáveis tenderam a avaliar o constructo em níveis inferiores ao de habilidade dos sujeitos, sugerindo a necessidade de itens avaliando níveis mais altos do constructo. Na análise de validade considerando outras medidas a tarefa de evocação imediata o escore total e evocação tardia apresentaram correlação com o total da tarefa de memória das figuras complexas de Rey. As tarefas de cópia correlacionaram-se com o total de cópia do teste das figuras complexas de Rey. A tarefa de evocação imediata o escore total e evocação tardia apresentaram correlação com o total do MEEM. A análise de covariância mostrou que a escolaridade exerce influência nos escores do RV. Assim, depois de controlada a escolaridade foi evidenciado que os controles tiveram melhor desempenho em todas as tarefas do RV, quando comparados aos pacientes com AVC-ACMHD. Na análise qualitativa, através do escalonamento e contraste dos escores, foi observado que o baixo desempenho dos pacientes com AVC se deve ao fato de que esses pacientes percebem muito mal o item, com pior controle motor, habilidade visuo-construtiva e capacidade de prestar atenção a detalhes. O resultado é uma menor aquisição da informações e as conseqüências são dificuldades na memória episódica não verbal . Os nossos resultados foram demonstrativos de que o RV da WMS- IV, além de culturalmente equivalente em termos de confiabilidade e validade, é adequado para a cultura dos sujeitos e pacientes avaliados em Ribeirão Preto, preciso e válido para o uso no Brasil. Saliente-se a necessidade de estudos normativos com esse subteste. / Tools for evaluation of non-verbal episodic memory are scarce. Furthermore, we consider the increasing need for efforts to cross-cultural adaptation of instruments of memory for our context. The subtest Visual Reproduction I and II is part of the Wechsler Memory Scale (WMS), and it is used worldwide scale and adapted to different cultures, and is considered the gold standard among assessment measures of memory. In the present study, we use the Visual Reproduction subtest of WMS in its fourth edition (WMS-IV). The Visual Reproduction (VR) is subdivided into three fields of research in visual memory (immediate recall, delayed recall and recognition) and an optional task to assess visual perception, constructive abilities and attention to detail (copy). Moreover, the score of each of the three domains can be contrasted evaluated in order to obtain information on retention, and the memory is better or worse than the constructive abilities, and finally, how the subject refers freely or need tracks to evoke the information learned. This version of the WMS-IV is a review of the WMS-III, whose studies have resulted in some changes in methodology and content, to facilitate the analysis of results, lower camest application and correction. Thus, to obtain the purposes of this research were carried out two studies: Study 1 was aimed at making cross-cultural adaptation of the subtest \"Visual Reproduction I and II - Wechsler Memory Scale - IV (WMS-IV)\" and present a version for use preliminary in Brazil and the second study consisted of an evaluation of its psychometric properties. The study included a three translators fluent in English, which made independent translations, translators two professional judges and two experts (a neurologist and a neuropsychologist) who performed the conceptual and item equivalence, semantic, and operational. 24 healthy subjects responded to the pretest, which consisted in the investigation of understanding and difficulty of the adapted version of the Visual Reproduction I and II. In the second study, participated in 62 healthy adults and 29 adults with stroke in the right hemisphere in the territory of the middle cerebral artery. All subjects were aged between 20 and 59 years and the responses were considered for analysis of reliability and validity based on statistical analysis of the classical theory (ANOVA, ANCOVA, Cronbach\'s alpha, and Pearsons correlation) and the modern theory testing (Item Theory Response IRT, the model of one parameter or Rasch method). The process of analyzing the psychometric properties following the methodology recommended by the American Educational Research Association [AERA], American Psychological Association [APA] and the National council on education measure in [NCME], 2008 - indicated by the publisher responsible for the copyright of the WMS-IV. In the reliability analysis, we investigated the internal consistency (Cronbach\'s alpha) and temporal stability (Pearsons correlation). To investigate the validity, were considered: the processes of response, the internal structure (Pearsons correlation and IRT), the relationship with other tools (Mini Mental State Exam- MMSE and Rey-Osterrieth Complex Figure Test (ROCF).) and the relationship with external variables (stroke in the right hemisphere in the territory of the middle cerebral artery, compared to healthy controls). The index of internal consistency overall subtest was 0.92 and test-retest stability showed significant correlation, except with the task of delayed recall. These results are similar to the original study, showing thus their equivalence. The results of the validity study showed that there is equivalence in terms of investigating the internal structure and content. Pearson\'s correlation coefficient showed that all the figures obtained significant correlation (p <0.001) and further correlated with each moment congruently the task. In investigating the internal structure by the Rasch method has been shown that the test is one-dimensional that the progression of theta over the response categories was as expected by the model, and show that the figure is the easier task of Figure 1 - immediate recall, and is harder to figure 5- for delayed recall. The theta correlation coefficients were greater than 0.5, showing good correlation. On the map of people-items showed that the variables tended to evaluate the construct at levels below the skill of the subjects, suggesting the need for items assessing higher levels of the construct. In the analysis of validity considering other measures, the total score of immediate recall and delayed recall correlated with the total of memory task of the Rey complex figure copy. The copy of the Visual Reproduction correlated with copy of Rey-Osterrieth Complex Figure Test (ROCF). The task of ROCF immediate recall of the total score and delayed recall correlated with total MMSE. Covariance analysis showed that education exercises influences on scores of the RV. So, after controlled the variable schooling, was evident that the controls performed better than patients with stroke on all Visual Reproduction subtest. The qualitative analysis via scaling contrast scores, shown that low performance of patients with stroke is due the fact they recognize the item very badly, the motor control, visuo-constructive ability and ability to pay attention to details is lowered. Its can occur, may be due apraxia, resulting in lower acquisition of the information, resulting in difficulties in non-verbal episodic memory. Our results showing that the Visual Reproduction subtest of the WMS-IV was considered culturally equivalent in terms of reliability and validity and is appropriate for culture of the subjects and patients evaluated in Ribeirão Preto, valid and reliable for use in Brazil. We emphasize the need of studies regarding to normative data for this subtest.

Instrumentos de avaliação da memória episódica não verbal são escassos. Além disto, consideramos a crescente necessidade de esforços para a adaptação transcultural de instrumentos de memória para nosso contexto. O subteste Visual Reproduction I e II (Reprodução Visual I e II) faz parte da Wechsler Memory Scale (WMS) e se trata de uma escala mundialmente utilizada e adaptada a diversas culturas, sendo considerada padrão ouro dentre as medidas de avaliação da memória. No presente estudo, utilizamos o subteste Reprodução Visual, da WMS na sua quarta edição (WMS-IV). O Reprodução Visual (RV) é subdividido em três domínios de investigação da memória visual (evocação imediata, evocação tardia e reconhecimento) e uma tarefa opcional para avaliação da percepção visual, habilidades construtivas e atenção aos detalhes (cópia). Além disto, o escore de cada um dos três domínios avaliados podem ser contrastados, de modo que se obtenham informações sobre a retenção, o quanto a memória é melhor ou pior do que as habilidades construtivas e, por último, o quão o sujeito evoca livremente ou precisa de pistas para evocar a informação aprendida. Esta versão da WMS-IV é uma revisão da WMS-III, cujos estudos resultaram em algumas alterações metodológicas e de conteúdo, no sentido de facilitar a análise dos resultados, diminuir os vieses de aplicação e correção. Desta forma, para atingir os propósitos desta pesquisa foram realizados dois estudos: o Estudo 1 teve como objetivo realizar a adaptação transcultural do subteste Visual Reproduction I and II - Wechsler Memory Scale IV (WMS-IV) e apresentar uma versão para uso preliminar no Brasil. O estudo 2 consistiu na avaliação das suas propriedades psicométricas. Participaram do estudo 1 três tradutores com fluência no inglês, que realizaram traduções independentes, dois tradutores profissionais e dois juízes especialistas (um neurologista e uma neuropsicóloga). Os juízes especialistas e um tradutor profissional investigaram a equivalência conceitual, semântica e operacional dos itens. Uma amostra de 24 sujeitos saudáveis responderam ao pré-teste, que consistiu na investigação da compreensão e dificuldade da versão adaptada do Reprodução Visual I e II. No estudo dois, participaram 62 adultos saudáveis e 29 adultos com Acidente vascular cerebral em hemisfério direito, no território da Artéria cerebral média (AVC-ACMHD). Os sujeitos tinham idade entre 20 e 59 anos e as respostas foram consideradas para análises de confiabilidade e validade baseadas em análises estatísticas da teoria clássica (ANOVA, ANCOVA, coeficiente alfa de Cronbach, e correlação de Pearson) e da teoria moderna de testagem (Teoria de Resposta ao Item (TRI) através do modelo de um parâmetro ou método de Rasch). O processo de análise das propriedades psicométricas utilizou a metodologia recomendada pelo American Educational Research Association [AERA], American Psychological Association [APA] e o National council on measure in education [NCME], 2008 indicada pela editora responsável pelos direitos autorais do WMS-IV. Na confiabilidade, foi investigada a consistência interna (coeficiente alfa de Cronbach) e a estabilidade temporal (correlação de Pearson). Na investigação da validade, foram investigados: os processos de resposta, a estrutura interna (correlação de Pearson, Teoria de resposta ao Item pelo método de Rash), a relação com outros instrumentos (Mini Exame do Estado Mental - MEEM e Figuras Complexas de Rey) e a relação com variáveis externas (AVC-ACMHD comparados a controles saudáveis). O índice de consistência interna do subteste foi de 0,92 e a estabilidade teste-reteste mostrou correlação significativa, exceto com a tarefa de evocação tardia. Esses resultados são similares aos do estudo original, sendo, portanto caracterizada a sua equivalência. Os resultados do estudo de validade mostraram que há equivalência em termos de conteúdo.A investigação da estrutura interna pelo coeficiente de correlação de Pearson evidenciou que todas as figuras obtiveram correlação significativa (p<0,001). Ainda mais: correlacionaram-se congruentemente durante toda a tarefa. Na investigação da estrutura interna pelo método de Rasch foi evidenciado que o teste é unidimensional, que a progressão de theta ao longo das categorias de resposta foram como o esperado pelo modelo. A TRI mostrou que a figura mais fácil é a figura 1 da tarefa de evocação imediata e a mais difícil é a figura 5 de evocação tardia. Os índices de correlação theta foram superiores a 0,5, mostrando correlação. No mapa de pessoas-itens as variáveis tenderam a avaliar o constructo em níveis inferiores ao de habilidade dos sujeitos, sugerindo a necessidade de itens avaliando níveis mais altos do constructo. Na análise de validade considerando outras medidas a tarefa de evocação imediata o escore total e evocação tardia apresentaram correlação com o total da tarefa de memória das figuras complexas de Rey. As tarefas de cópia correlacionaram-se com o total de cópia do teste das figuras complexas de Rey. A tarefa de evocação imediata o escore total e evocação tardia apresentaram correlação com o total do MEEM. A análise de covariância mostrou que a escolaridade exerce influência nos escores do RV. Assim, depois de controlada a escolaridade foi evidenciado que os controles tiveram melhor desempenho em todas as tarefas do RV, quando comparados aos pacientes com AVC-ACMHD. Na análise qualitativa, através do escalonamento e contraste dos escores, foi observado que o baixo desempenho dos pacientes com AVC se deve ao fato de que esses pacientes percebem muito mal o item, com pior controle motor, habilidade visuo-construtiva e capacidade de prestar atenção a detalhes. O resultado é uma menor aquisição da informações e as conseqüências são dificuldades na memória episódica não verbal . Os nossos resultados foram demonstrativos de que o RV da WMS- IV, além de culturalmente equivalente em termos de confiabilidade e validade, é adequado para a cultura dos sujeitos e pacientes avaliados em Ribeirão Preto, preciso e válido para o uso no Brasil. Saliente-se a necessidade de estudos normativos com esse subteste. / Tools for evaluation of non-verbal episodic memory are scarce. Furthermore, we consider the increasing need for efforts to cross-cultural adaptation of instruments of memory for our context. The subtest Visual Reproduction I and II is part of the Wechsler Memory Scale (WMS), and it is used worldwide scale and adapted to different cultures, and is considered the gold standard among assessment measures of memory. In the present study, we use the Visual Reproduction subtest of WMS in its fourth edition (WMS-IV). The Visual Reproduction (VR) is subdivided into three fields of research in visual memory (immediate recall, delayed recall and recognition) and an optional task to assess visual perception, constructive abilities and attention to detail (copy). Moreover, the score of each of the three domains can be contrasted evaluated in order to obtain information on retention, and the memory is better or worse than the constructive abilities, and finally, how the subject refers freely or need tracks to evoke the information learned. This version of the WMS-IV is a review of the WMS-III, whose studies have resulted in some changes in methodology and content, to facilitate the analysis of results, lower camest application and correction. Thus, to obtain the purposes of this research were carried out two studies: Study 1 was aimed at making cross-cultural adaptation of the subtest \"Visual Reproduction I and II - Wechsler Memory Scale - IV (WMS-IV)\" and present a version for use preliminary in Brazil and the second study consisted of an evaluation of its psychometric properties. The study included a three translators fluent in English, which made independent translations, translators two professional judges and two experts (a neurologist and a neuropsychologist) who performed the conceptual and item equivalence, semantic, and operational. 24 healthy subjects responded to the pretest, which consisted in the investigation of understanding and difficulty of the adapted version of the Visual Reproduction I and II. In the second study, participated in 62 healthy adults and 29 adults with stroke in the right hemisphere in the territory of the middle cerebral artery. All subjects were aged between 20 and 59 years and the responses were considered for analysis of reliability and validity based on statistical analysis of the classical theory (ANOVA, ANCOVA, Cronbach\'s alpha, and Pearsons correlation) and the modern theory testing (Item Theory Response IRT, the model of one parameter or Rasch method). The process of analyzing the psychometric properties following the methodology recommended by the American Educational Research Association [AERA], American Psychological Association [APA] and the National council on education measure in [NCME], 2008 - indicated by the publisher responsible for the copyright of the WMS-IV. In the reliability analysis, we investigated the internal consistency (Cronbach\'s alpha) and temporal stability (Pearsons correlation). To investigate the validity, were considered: the processes of response, the internal structure (Pearsons correlation and IRT), the relationship with other tools (Mini Mental State Exam- MMSE and Rey-Osterrieth Complex Figure Test (ROCF).) and the relationship with external variables (stroke in the right hemisphere in the territory of the middle cerebral artery, compared to healthy controls). The index of internal consistency overall subtest was 0.92 and test-retest stability showed significant correlation, except with the task of delayed recall. These results are similar to the original study, showing thus their equivalence. The results of the validity study showed that there is equivalence in terms of investigating the internal structure and content. Pearson\'s correlation coefficient showed that all the figures obtained significant correlation (p <0.001) and further correlated with each moment congruently the task. In investigating the internal structure by the Rasch method has been shown that the test is one-dimensional that the progression of theta over the response categories was as expected by the model, and show that the figure is the easier task of Figure 1 - immediate recall, and is harder to figure 5- for delayed recall. The theta correlation coefficients were greater than 0.5, showing good correlation. On the map of people-items showed that the variables tended to evaluate the construct at levels below the skill of the subjects, suggesting the need for items assessing higher levels of the construct. In the analysis of validity considering other measures, the total score of immediate recall and delayed recall correlated with the total of memory task of the Rey complex figure copy. The copy of the Visual Reproduction correlated with copy of Rey-Osterrieth Complex Figure Test (ROCF). The task of ROCF immediate recall of the total score and delayed recall correlated with total MMSE. Covariance analysis showed that education exercises influences on scores of the RV. So, after controlled the variable schooling, was evident that the controls performed better than patients with stroke on all Visual Reproduction subtest. The qualitative analysis via scaling contrast scores, shown that low performance of patients with stroke is due the fact they recognize the item very badly, the motor control, visuo-constructive ability and ability to pay attention to details is lowered. Its can occur, may be due apraxia, resulting in lower acquisition of the information, resulting in difficulties in non-verbal episodic memory. Our results showing that the Visual Reproduction subtest of the WMS-IV was considered culturally equivalent in terms of reliability and validity and is appropriate for culture of the subjects and patients evaluated in Ribeirão Preto, valid and reliable for use in Brazil. We emphasize the need of studies regarding to normative data for this subtest.

[pt] Diversos estudos apontam o efeito do nível de escolaridade parental no desenvolvimento das funções cognitivas, em especial a linguagem e as funções executivas. Evidenciam a importância da interação entre o cuidador e a criança, a qualidade da estimulação e a promoção de experiências de desenvolvimento, propiciadas a criança, como fundamentais para o desenvolvimento das funções executivas. Há poucos estudos desse efeito no desenvolvimento de crianças brasileiras. O objetivo da dissertação foi investigar o efeito do nível de escolaridade dos pais, separadamente, no desempenho em tarefas de memória de longo prazo, memória de trabalho, controle inibitório e flexibilidade cognitiva de crianças e adolescentes com baixo nível socioeconômico na cidade do Rio de Janeiro. Participaram do estudo 352 crianças entre 7 a 15 anos de escolas privadas com perfil de baixo nível socioeconômico na cidade do Rio de Janeiro. Os instrumentos utilizados foram a Figura Complexa de Rey, a Aprendizagem auditivo verbal de Rey, o paradigma de Stroop e as tarefas de Fluência Verbal fonêmica e semântica. Os resultados mostraram efeitos para a escolaridade de ambos os pais. Resultados sistemáticos aconteceram na fluência verbal, na faixa de 9-10 anos. Não foram encontrados efeitos significativos em controle inibitório e memória de trabalho. O efeito da escolaridade parental apareceu de forma sistemática em funções executivas, mas não em outras funções, em uma amostra homogênea, o que levanta a ideia de que outros fatores como a renda e a cultura, se somam ao efeito ambiental no desenvolvimento cognitivo. / [en] Several studies demonstrated the effect of parents educational level in the development of cognitive functions, especially language and executive functions. Highlight the importance of interaction between the caregiver and the child, the quality of stimulation and promotion of development experiences afforded the child, as fundamental for the development of executive functions. There are few studies of this effect in the development of Brazilian children. The objective of the study is to analyze the effect of the education level of parents, separately, in the cognitive performance of long-term memory, working memory, inhibitory control and cognitive flexibility in children and adolescents living at Rio de Janeiro with low socioeconomic status. The study included 352 children between 7-15 years of private schools with low socioeconomic profile students of city of Rio de Janeiro. The instruments used were the Rey–Osterrieth Complex Figure Test, the Rey Auditory Verbal Learning Test, the Stroop test (Victoria Version) and Verbal Fluency phonemic and semantic. The results showed effects on education of both parents. Systematic results happened in verbal fluency, in the 9-10 year group. There were no significant effects on inhibitory control and working memory. The effect of parental education appeared systematically in executive functions, but not in other functions, raises the idea that other factors such as income and culture add to the environmental effect on cognitive development.

La maladie d’Alzheimer (MA) est à l’origine de la majorité des cas de démence chez les personnes âgées. Son diagnostic précoce est essentiel pour mieux comprendre les mécanismes cérébraux sous-tendant la manifestation phénotypique de la maladie et développer des interventions conséquentes. Le fait d’étudier des individus à risque de développer la MA, par exemple ceux présentant un déclin cognitif subjectif (DCS) ou un trouble cognitif léger (TCL), offre l’opportunité d’examiner les processus neuropathophysiologiques qui précèdent le stade démentiel. Cela permettrait, entre autres, d’identifier des biomarqueurs avant-coureurs de la maladie. Cette thèse avait pour but d’investiguer la présence d’hyperactivation cérébrale chez des individus à risque de développer la MA, et d’examiner les réseaux cérébraux fonctionnels associés à l’hyperactivation. L’hyperactivation se définit par la présence de niveaux supérieurs d’activation cérébrale chez des personnes faisant partie de groupes à risque pour la MA (p.ex. DCS ou TCL), comparativement à des participants contrôles cognitivement sains. L’hyperactivation est le plus souvent mesurée par l’imagerie par résonance magnétique fonctionnelle (IRMf) en condition de réalisation de tâche. Dans cette thèse, le lecteur ou la lectrice sera d’abord exposée aux études ayant utilisé l’IRMf pour examiner les patrons d’activation cérébrale et de connectivité fonctionnelle chez les individus ayant reçu un diagnostic clinique de MA, de TCL ou présentant un DCS. Les modèles théoriques découlant de ces études seront ensuite présentés. Afin de mieux comprendre le phénomène d’hyperactivation et sa relation avec les patrons de connectivité fonctionnelle, les divers enjeux scientifiques qui demeurent à être abordés seront ensuite décrits (Chapitre 1). Trois articles exposant les études empiriques formant le corps de la thèse seront ensuite présentés. La première étude avait pour but de documenter la présence, la localisation et l’évolution longitudinale de l’hyperactivation iv associée à une tâche de mémoire épisodique chez des individus qui rencontrent les critères de TCL et qui ont ultérieurement progressé vers une démence (Chapitre 2). La deuxième étude visait à déterminer la trajectoire de l’activation cérébrale associée à une tâche de mémoire associative en fonction du degré de sévérité de la maladie chez un groupe d’individus à risque de développer la MA. Elle avait également pour but de déterminer la présence d’hyperactivation chez des personnes rencontrant les critères de DCS plus (ou DCS+), qui sont des individus présentant une plainte de mémoire ainsi que des marqueurs génétiques et/ou de neurodégénérescence pour la MA (Chapitre 3). La troisième étude avait pour but d’examiner les réseaux cérébraux fonctionnels associés aux régions montrant de l’hyperactivation chez des individus à risque de développer la MA. Elle avait également pour objectif d’évaluer comment l’hyperactivation et ces réseaux cérébraux fonctionnels sont reliés aux performances en mémoire (Chapitre 4). Les résultats découlant de l’étude 1 ont permis de mettre en évidence la présence d’hyperactivation chez des individus présentant un TCL et ayant ultérieurement progressé vers le stade de démence. Les trouvailles de l’étude 2 indiquent qu’une fonction quadratique décrit la relation entre des indices de sévérité de la maladie et l’activation pariétale supérieure gauche chez un groupe d’individus à risque de développer la MA (DCS+ et TCL). Par ailleurs, des niveaux supérieurs d’activation, c’est-à-dire de l’hyperactivation, étaient retrouvés dans les hippocampes + et plusieurs régions temporo-pariétales dans le groupe d’individus DCS . Une hypoactivation pariétale supérieure gauche était plutôt retrouvée chez les individus TCL. Enfin, les résultats de l’étude 3 indiquent que l’hyperactivation de régions prédéterminées est associée à la dysfonction de réseaux cérébraux fonctionnels impliqués dans les processus de mémoire associative dans le DCS+ et le TCL. De plus, ces interactions hyperactivation-réseaux étaient associées à une symptomatologie cognitive croissante. Les implications de cette thèse et ses limites sont abordées dans la discussion (Chapitre 5). / Alzheimer's disease (AD) is the most common cause of dementia in older adults. Its early diagnosis is essential to better understand the brain mechanisms underlying the phenotypical manifestation of the disease and develop consequent interventions. The study of individuals at risk of AD, for example those presenting with subjective cognitive decline (SCD) or mild cognitive impairment (MCI), offers the opportunity to examine the neuropathophysiological processes preceding the dementia stage. This would allow, among other things, to identify early biomarkers of the disease. The general aim of this thesis was to determine the presence of cerebral hyperactivation and to assess functional brain networks associated with hyperactivation. Hyperactivation is defined by the presence of higher levels of brain activation in individuals at risk of AD (i.e. SCD, MCI) in comparison to cognitively healthy controls. Hyperactivation is most often measured with functional magnetic resonance imaging (fMRI) while participants perform a cognitive task. In this thesis, the reader will first be exposed to the studies which used fMRI to examine patterns of brain activation and connectivity in individuals with a clinical diagnosis of AD, MCI or presenting with SCD. Theoretical models resulting from these studies will then be presented. The scientific issues remaining to be addressed to better understand the phenomenon of hyperactivation and its relation to functional brain networks will then be described (Chapter 1). Three empirical studies forming the core of this thesis will be presented. The first study aimed to assess the presence, localization and longitudinal evolution of hyperactivation associated with an episodic memory task in individuals meeting criteria for MCI and having subsequently progressed towards dementia (Chapter 2). The second study aimed to determine the trajectory of brain activation associated with an associative memory task as a function of disease severity in a group of individuals at risk of AD. It also aimed to determine if hyperactivation is present in viii participants meeting criteria for SCD plus (or SCD+), who are individuals presenting with memory complaint in addition to genetic and/or neurodegeneresence markers of AD (Chapter 3). The third and last study aimed to examine patterns of functional connectivity related to regions of hyperactivation, and to assess how hyperactivation and its associated functional networks relate to memory performance in individuals at risk of AD (Chapter 4). Results from the first study highlighted the presence of hyperactivation in individuals with MCI who subsequently progressed to the dementia stage. Findings from the second study revealed a quadratic function describing the relationship between proxies of disease severity (neurodegeneration, memory performance) and left superior parietal activation in a group of individuals at risk of AD (SCD+ and MCI). Moreover, higher levels of activation, i.e. hyperactivation, were found in hippocampal and temporo-parietal regions in the SCD+ group. Hypoactivation was rather found in the left superior parietal area in the MCI group. Finally, results from the third study revealed that hyperactivation of predetermined regions was associated with dysfunction of functional brain networks underlying associative memory in SCD+ and MCI. Moreover, these hyperactivation-network interactions were associated with increasing symptomatology. The implications of this thesis and its limits are addressed in the discussion section (Chapter 5).

La mémoire épisodique est la fonction neurocognitive humaine permettant de se souvenir des événements passés situés dans leur contexte spatio-temporel ainsi que de se rappeler d'exécuter des actions futures spécifiques et d'imaginer des événements futurs variés. Comme d'autres capacités complexes, son développement est lié à d'autres fonctions telles que les fonctions exécutives et la théorie de l'esprit. Elle peut être évaluée avec du matériel de laboratoire nécessitant une mémorisation de nouvelles informations et d'actions futures à réaliser plus tard (mémoires rétrospective et prospective, respectivement), ainsi que via des événements personnels (rappel du passé et imagination du futur ou mémoire autobiographique passée et future, respectivement). L'objectif de cette thèse était, d'une part, de comparer les aspects passé et futur de la mémoire épisodique dans une approche développementale de l'enfant d'âge scolaire au jeune adulte, tout en explorant les mécanismes sous-jacents. D'autre part, le but était également de comparer des tâches autobiographiques et des tâches de laboratoire plus écologiques en réalité virtuelle.Les résultats suggèrent un développement plus progressif de l'aspect futur de la mémoire épisodique (plus de différences chez les enfants), tandis que l'aspect passé semble être bien développé à l'adolescence. Concernant les mécanismes, les performances aux tâches autobiographique et en réalité virtuelle (corrélées entre elles) sont liées aux fonctions exécutives et aux capacités narratives ; de plus, les capacités de rappel lors du test de réalité virtuelle dépendent des fonctions exécutives, la mémoire autobiographique passée et future et la théorie de l'esprit (seulement pour le futur), tandis que les capacités de mémoire autobiographique dépendent de la mémoire du futur en réalité virtuelle en plus des fonctions exécutives et de l'âge.Ces données démontrent que malgré un développement plus progressif de l'aspect futur que passé de la mémoire épisodique, le fonctionnement mnésique dans des environnements virtuels est comparable à la mémoire au quotidien, compte tenu de leurs inter-corrélations et de leurs mécanismes au moins en partie communs. Par ailleurs, les tâches de réalité virtuelle peuvent trouver toute leur utilité dans l'évaluation des patients pédiatriques neurologiques dont les déficits mnésiques peuvent être plus ou moins subtils et se refléter plus aux contextes quotidiens qu'aux contextes des évaluations de type papier-crayon. / Episodic memory is the uniquely human neurocognitive function that enables us to recall past events situated in their spatio-temporal context and to remember to carry out specific future actions as well as imagine various personal future events. As all complex abilities, its functioning is linked to other cognitive capacities such as executive functions and theory of mind. It can be assessed with laboratory-based materials requiring the memorization of information and future actions to be recalled later (retrospective and prospective memory, respectively) and via personal events (recalling past ones and imagining future ones or past and future autobiographical memory, respectively). The aim of this thesis was, on the one hand, to compare both past and future aspects of episodic memory functioning in a wide developmental age span (from young schoolchildren to young adults), and to explore underlying developmental mechanisms. On the other hand, we also aimed to compare personal events¿ (autobiographical) tasks with more ecological laboratory tasks using virtual reality. Results suggest a more progressive development of the future aspect of episodic memory (more differences between children), whereas both retrospective and past autobiographical memory seem to be quite functional by adolescence. Regarding mechanisms, both autobiographical and virtual reality performance, in addition to correlating with each other, are linked to executive functions and narrative abilities; also, memory abilities assessed via virtual reality depend on executive functions, past and future autobiographical memory and (only future memory) on theory of mind performance, whereas autobiographical memory abilities depend on virtual reality-based future memory in addition to executive functions and age. Our data demonstrate that despite a more progressive development of the future aspect of episodic memory than of its past aspect, memory functioning in virtual environments is indeed comparable to daily life memory, as these abilities are strongly inter-linked and have at least partly common mechanisms. Also, virtual reality tasks can be used for memory assessments in pediatric neurological patients whose potential memory deficits can be more or less subtle and thus more detectable in daily life contexts as opposed to paper-and-pencil types of contexts.

Indiana University-Purdue University Indianapolis (IUPUI) / Alzheimer's disease (AD) is a national priority, with nearly six million Americans affected at an annual cost of $200 billion and no available cure. A better understanding of the mechanisms underlying AD is crucial to combat its high and rising incidence and burdens. Most cases of AD are thought to have a complex etiology with numerous genetic and environmental factors influencing susceptibility. Recent genome-wide association studies (GWAS) have confirmed roles for several hypothesized genes and have discovered novel loci associated with disease risk. However, most GWAS-implicated genetic variants have displayed modest individual effects on disease risk and together leave substantial heritability and pathophysiology unexplained. As a result, new paradigms focusing on biological pathways have emerged, drawing on the hypothesis that complex diseases may be influenced by collective effects of multiple variants – of a variety of effect sizes, directions, and frequencies – within key biological pathways. A variety of tools have been developed for pathway-based statistical analysis of GWAS data, but consensus approaches have not been systematically determined. We critically review strategies for genetic pathway analysis, synthesizing extant concepts and methodologies to guide application and future development. We then apply pathway-based approaches to complement GWAS of key AD-related endophenotypes, focusing on two early, hallmark features of disease, episodic memory impairment and brain deposition of amyloid-β. Using GWAS and pathway analysis, we confirmed the association of APOE (apolipoprotein E) and discovered additional genetic modulators of memory functioning and amyloid-β deposition in AD, including pathways related to long-term potentiation, cell adhesion, inflammation, and NOTCH signaling. We also identified genetic associations to amyloid-β deposition that have classically been understood to mediate learning and memory, including the BCHE gene and signaling through the epidermal growth factor receptor. These findings validate the use of pathway analysis in complex diseases and illuminate novel genetic mechanisms of AD, including several pathways at the intersection of disease-related pathology and cognitive decline which represent targets for future studies. The complexity of the AD genetic architecture also suggests that biomarker and treatment strategies may require simultaneous targeting of multiple pathways to effectively combat disease onset and progression.